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BACKGROUND: Monitoring therapeutic efficacy is important to ensure the efficacy of artemisinin-based combination therapy (ACT) for malaria. The current first-line treatment for uncomplicated malaria recommended by the National Malaria Control Program in Niger is artemether-lumefantrine (AL). In 2020, an in vivo study was carried out to evaluate clinical and parasitological responses to AL as well as the molecular resistance to the drug in three sentinel sites: Agadez, Tessaoua and Gaya, in Niger. METHODS: A multi-center, single-arm trial was conducted according to the 28-day World Health Organization (WHO) 2009 therapeutic efficacy study protocol. Children between 6 months and 15 years with confirmed uncomplicated Plasmodium falciparum infection and 1000-200,000 asexual parasites/µL of blood were enrolled and followed up for 28 days. Uncorrected and PCR-corrected efficacy results at day 28 were calculated, and molecular correction was performed by genotyping the msp1, msp2, and glurp genes. The pfk13, pfdhfr, pfdhps, pfcrt and pfmdr genes were analyzed by PCR and Sanger sequencing. The Kaplan-Meier curve assessed parasite clearance. RESULTS: A total of 255 patients were enrolled in the study. The adequate clinical and parasitological response after PCR correction was 98.9% (95% CI 96.4-101.0%), 92.2% (85.0-98.5%) and 97.1% (93.1-101.0%) in Gaya, Tessaoua and Agadez, respectively. No adverse events were observed. Ten mutations (SNP) were found, including 7 synonyms (K248K, G690G, E691E, E612E, C469C, G496G, P718P) and 3 non-synonyms (N594K, R255K, V714S). Two mutations emerged: N594K and V714S. The R255K mutation detected in Southeast Asia was also detected. The pfdhpsK540E and pfdhfrI164L mutations associated with high levels of resistance are absent. There is a reversal of chloroquine resistance. CONCLUSION: The study findings indicate that AL is effective and well tolerated for the treatment of uncomplicated malaria in three sites in Niger. The emergence of a pfk13 mutation requires additional testing such as the Ring Stage Assay and CRISPR/Cas9 to confirm the role of these emerging mutations. Trial registration NCT05070520, October 7, 2021.
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Antimaláricos , Combinación Arteméter y Lumefantrina , Malaria Falciparum , Plasmodium falciparum , Combinación Arteméter y Lumefantrina/uso terapéutico , Malaria Falciparum/tratamiento farmacológico , Antimaláricos/uso terapéutico , Antimaláricos/efectos adversos , Preescolar , Humanos , Niger , Niño , Lactante , Adolescente , Masculino , Femenino , Plasmodium falciparum/efectos de los fármacos , Plasmodium falciparum/genética , Resistencia a Medicamentos/genéticaRESUMEN
BACKGROUND: Artemisinin-based combination therapy (ACT) is the most effective treatment for malaria, and has significantly reduced morbimortality. Polymorphisms associated with the Plasmodium falciparum Kelch gene (Pfkelch13) have been associated with delayed parasite clearance even with ACT treatment. METHODS: The Pfkelch13 gene was sequenced from P. falciparum infected patients (n = 159) with uncomplicated malaria in Niger. An adequate clinical and parasitological response (ACPR) was reported in 155 patients. Four (n = 4) patients had treatment failure (TF) that were not reinfections-two of which had late parasitological failures (LPF) and two had late clinical failures (LCF). RESULTS: Thirteen single nucleotide polymorphisms (SNPs) were identified of which seven were non-synonymous (C469R, T508S, R515T, A578S, I465V, I437V, F506L,), and three were synonymous (P443P, P715P, L514L). Three SNP (C469R, F506L, P715P) were present before ACT treatment, while seven mutations (C469R, T508S, R515T, L514L, P443P, I437V, I465V) were selected by artemether/lumefantrine (AL)-five of which were non-synonymous (C469R, T508S, R515T, I437V, I465V). Artesunate/amodiaquine (ASAQ) has selected any mutation. One sample presented three cumulatively non-synonymous SNPs-C469R, T508S, R515T. CONCLUSIONS: This study demonstrates intra-host selection of Pfkelch13 gene by AL. The study highlights the importance of LCF and LPF parasites in the selection of resistance to ACT. Further studies using gene editing are required to confirm the potential implication of resistance to ACT with the most common R515T and T508S mutations. It would also be important to elucidate the role of cumulative mutations.
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Antimaláricos , Artemisininas , Malaria Falciparum , Humanos , Plasmodium falciparum/genética , Antimaláricos/uso terapéutico , Combinación Arteméter y Lumefantrina/uso terapéutico , Artemisininas/uso terapéutico , Niger , Combinación de Medicamentos , Arteméter/uso terapéutico , Amodiaquina/uso terapéutico , Malaria Falciparum/tratamiento farmacológico , Insuficiencia del Tratamiento , Polimorfismo de Nucleótido SimpleRESUMEN
[This corrects the article DOI: 10.1371/journal.pmed.1003720.].
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BACKGROUND: Nutritional status may play a role in infant immune development. To identify potential boosters of immunogenicity in low-income countries where oral vaccine efficacy is low, we tested the effect of prenatal nutritional supplementation on immune response to 3 doses of a live oral rotavirus vaccine. METHODS AND FINDINGS: We nested a cluster randomized trial within a double-blind, placebo-controlled randomized efficacy trial to assess the effect of 3 prenatal nutritional supplements (lipid-based nutrient supplement [LNS], multiple micronutrient supplement [MMS], or iron-folic acid [IFA]) on infant immune response (n = 53 villages and 1,525 infants with valid serology results: 794 in the vaccine group and 731 in the placebo group). From September 2015 to February 2017, participating women received prenatal nutrient supplement during pregnancy. Eligible infants were then randomized to receive 3 doses of an oral rotavirus vaccine or placebo at 6-8 weeks of age (mean age: 6.3 weeks, 50% female). Infant sera (pre-Dose 1 and 28 days post-Dose 3) were analyzed for anti-rotavirus immunoglobulin A (IgA) using enzyme-linked immunosorbent assay (ELISA). The primary immunogenicity end point, seroconversion defined as ≥3-fold increase in IgA, was compared in vaccinated infants among the 3 supplement groups and between vaccine/placebo groups using mixed model analysis of variance procedures. Seroconversion did not differ by supplementation group (41.1% (94/229) with LNS vs. 39.1% (102/261) with multiple micronutrients (MMN) vs. 38.8% (118/304) with IFA, p = 0.91). Overall, 39.6% (n = 314/794) of infants who received vaccine seroconverted, compared to 29.0% (n = 212/731) of infants who received placebo (relative risk [RR]: 1.36; 95% confidence interval [CI]: 1.18, 1.57, p < 0.001). This study was conducted in a high rotavirus transmission setting. Study limitations include the absence of an immune correlate of protection for rotavirus vaccines, with the implications of using serum anti-rotavirus IgA for the assessment of immunogenicity and efficacy in low-income countries unclear. CONCLUSIONS: This study showed no effect of the type of prenatal nutrient supplementation on immune response in this setting. Immune response varied depending on previous exposure to rotavirus, suggesting that alternative delivery modalities and schedules may be considered to improve vaccine performance in high transmission settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT02145000.
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Suplementos Dietéticos , Ácido Fólico/administración & dosificación , Inmunogenicidad Vacunal , Hierro/administración & dosificación , Lípidos/administración & dosificación , Micronutrientes/administración & dosificación , Vacunas contra Rotavirus/inmunología , Rotavirus/inmunología , Análisis por Conglomerados , Método Doble Ciego , Femenino , Humanos , Lactante , Masculino , Niger , Embarazo , Fenómenos Fisiologicos de la Nutrición Prenatal , Infecciones por Rotavirus/prevención & control , Vacunas contra Rotavirus/administración & dosificación , Vacunas Atenuadas/administración & dosificaciónRESUMEN
BACKGROUND: Rotavirus vaccination is recommended in all countries to reduce the burden of diarrhea-related morbidity and mortality in children. In resource-limited settings, rotavirus vaccination in the national immunization program has important cost implications, and evidence for protection beyond the first year of life and against the evolving variety of rotavirus strains is important. We assessed the extended and strain-specific vaccine efficacy of a heat-stable, affordable oral rotavirus vaccine (Rotasiil, Serum Institute of India, Pune, India) against severe rotavirus gastroenteritis (SRVGE) among healthy infants in Niger. METHODS AND FINDINGS: From August 2014 to November 2015, infants were randomized in a 1:1 ratio to receive 3 doses of Rotasiil or placebo at approximately 6, 10, and 14 weeks of age. Episodes of gastroenteritis were assessed through active and passive surveillance and graded using the Vesikari score. The primary endpoint was vaccine efficacy of 3 doses of vaccine versus placebo against a first episode of laboratory-confirmed SRVGE (Vesikari score ≥ 11) from 28 days after dose 3, as previously reported. At the time of the primary analysis, median age was 9.8 months. In the present paper, analyses of extended efficacy were undertaken for 3 periods (28 days after dose 3 to 1 year of age, 1 to 2 years of age, and the combined period 28 days after dose 3 to 2 years of age) and by individual rotavirus G type. Among the 3,508 infants included in the per-protocol efficacy analysis (mean age at first dose 6.5 weeks; 49% male), the vaccine provided significant protection against SRVGE through the first year of life (3.96 and 9.98 cases per 100 person-years for vaccine and placebo, respectively; vaccine efficacy 60.3%, 95% CI 43.6% to 72.1%) and over the entire efficacy follow-up period up to 2 years of age (2.13 and 4.69 cases per 100 person-years for vaccine and placebo, respectively; vaccine efficacy 54.7%, 95% CI 38.1% to 66.8%), but the difference was not statistically significant in the second year of life. Up to 2 years of age, rotavirus vaccination prevented 2.56 episodes of SRVGE per 100 child-years. Estimates of efficacy against SRVGE by individual rotavirus genotype were consistent with the overall protective efficacy. Study limitations include limited generalizability to settings with administration of oral polio virus due to low concomitant administration, limited power to assess vaccine efficacy in the second year of life owing to a low number of events among older children, potential bias due to censoring of placebo children at the time of study vaccine receipt, and suboptimal adapted severity scoring based on the Vesikari score, which was designed for use in settings with high parental literacy. CONCLUSIONS: Rotasiil provided protection against SRVGE in infants through an extended follow-up period of approximately 2 years. Protection was significant in the first year of life, when the disease burden and risk of death are highest, and against a changing pattern of rotavirus strains during the 2-year efficacy period. Rotavirus vaccines that are safe, effective, and protective against multiple strains represent the best hope for preventing the severe consequences of rotavirus infection, especially in resource-limited settings, where access to care may be limited. Studies such as this provide valuable information for the planning of national immunization programs and future vaccine development. TRIAL REGISTRATION: ClinicalTrials.gov NCT02145000.
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Gastroenteritis/prevención & control , Gastroenteritis/virología , Infecciones por Rotavirus/prevención & control , Vacunas contra Rotavirus/administración & dosificación , Vacunas contra Rotavirus/inmunología , Rotavirus/inmunología , Preescolar , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Programas de Inmunización , Lactante , Masculino , Niger , Placebos , Vacunas Atenuadas/administración & dosificación , Vacunas Atenuadas/inmunologíaRESUMEN
BACKGROUND: Each year, rotavirus gastroenteritis is responsible for about 37% of deaths from diarrhea among children younger than 5 years of age worldwide, with a disproportionate effect in sub-Saharan Africa. METHODS: We conducted a randomized, placebo-controlled trial in Niger to evaluate the efficacy of a live, oral bovine rotavirus pentavalent vaccine (BRV-PV, Serum Institute of India) to prevent severe rotavirus gastroenteritis. Healthy infants received three doses of the vaccine or placebo at 6, 10, and 14 weeks of age. Episodes of gastroenteritis were assessed through active and passive surveillance and were graded on the basis of the score on the Vesikari scale (which ranges from 0 to 20, with higher scores indicating more severe disease). The primary end point was the efficacy of three doses of vaccine as compared with placebo against a first episode of laboratory-confirmed severe rotavirus gastroenteritis (Vesikari score, ≥11) beginning 28 days after dose 3. RESULTS: Among the 3508 infants who were included in the per-protocol efficacy analysis, there were 31 cases of severe rotavirus gastroenteritis in the vaccine group and 87 cases in the placebo group (2.14 and 6.44 cases per 100 person-years, respectively), for a vaccine efficacy of 66.7% (95% confidence interval [CI], 49.9 to 77.9). Similar efficacy was seen in the intention-to-treat analyses, which showed a vaccine efficacy of 69.1% (95% CI, 55.0 to 78.7). There was no significant between-group difference in the risk of adverse events, which were reported in 68.7% of the infants in the vaccine group and in 67.2% of those in the placebo group, or in the risk of serious adverse events (in 8.3% in the vaccine group and in 9.1% in the placebo group); there were 27 deaths in the vaccine group and 22 in the placebo group. None of the infants had confirmed intussusception. CONCLUSIONS: Three doses of BRV-PV, an oral rotavirus vaccine, had an efficacy of 66.7% against severe rotavirus gastroenteritis among infants in Niger. (Funded by Médecins sans Frontières Operational Center and the Kavli Foundation; ClinicalTrials.gov number, NCT02145000 .).
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Gastroenteritis/prevención & control , Infecciones por Rotavirus/prevención & control , Vacunas contra Rotavirus , Administración Oral , Animales , Bovinos , Heces/virología , Femenino , Gastroenteritis/epidemiología , Gastroenteritis/virología , Humanos , Incidencia , Lactante , Estimación de Kaplan-Meier , Masculino , Niger , Rotavirus/aislamiento & purificación , Vacunas contra Rotavirus/efectos adversos , Vacunas contra Rotavirus/economía , Vacunas AtenuadasRESUMEN
BACKGROUND: High-quality evidence supporting a community-based treatment protocol for children with severe acute malnutrition, including routine antibiotic use at admission to a nutritional treatment program, remains limited. In view of the costs and consequences of emerging resistance associated with routine antibiotic use, more evidence is required to support this practice. METHODS: In a double-blind, placebo-controlled trial in Niger, we randomly assigned children who were 6 to 59 months of age and had uncomplicated severe acute malnutrition to receive amoxicillin or placebo for 7 days. The primary outcome was nutritional recovery at or before week 8. RESULTS: A total of 2412 children underwent randomization, and 2399 children were included in the analysis. Nutritional recovery occurred in 65.9% of children in the amoxicillin group (790 of 1199) and in 62.7% of children in the placebo group (752 of 1200). There was no significant difference in the likelihood of nutritional recovery (risk ratio for amoxicillin vs. placebo, 1.05; 95% confidence interval [CI], 0.99 to 1.12; P=0.10). In secondary analyses, amoxicillin decreased the risk of transfer to inpatient care by 14% (26.4% in the amoxicillin group vs. 30.7% in the placebo group; risk ratio, 0.86; 95% CI, 0.76 to 0.98; P=0.02). CONCLUSIONS: We found no benefit of routine antibiotic use with respect to nutritional recovery from uncomplicated severe acute malnutrition in Niger. In regions with adequate infrastructure for surveillance and management of complications, health care facilities could consider eliminating the routine use of antibiotics in protocols for the treatment of uncomplicated severe acute malnutrition. (Funded by Médecins sans Frontières Operational Center Paris; ClinicalTrials.gov number, NCT01613547.).
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Amoxicilina/uso terapéutico , Antibacterianos/uso terapéutico , Desnutrición Aguda Severa/tratamiento farmacológico , Infecciones Bacterianas/complicaciones , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/epidemiología , Preescolar , Método Doble Ciego , Femenino , Humanos , Lactante , Masculino , Estado Nutricional , Prevalencia , Desnutrición Aguda Severa/complicaciones , Desnutrición Aguda Severa/fisiopatología , Insuficiencia del Tratamiento , Aumento de Peso/efectos de los fármacosRESUMEN
BACKGROUND: Antibiotic prophylaxis for contacts of meningitis cases is not recommended during outbreaks in the African meningitis belt. We assessed the effectiveness of single-dose oral ciprofloxacin administered to household contacts and in village-wide distributions on the overall attack rate (AR) in an outbreak of meningococcal meningitis. METHODS AND FINDINGS: In this 3-arm, open-label, cluster-randomized trial during a meningococcal meningitis outbreak in Madarounfa District, Niger, villages notifying a suspected case were randomly assigned (1:1:1) to standard care (the control arm), single-dose oral ciprofloxacin for household contacts within 24 hours of case notification, or village-wide distribution of ciprofloxacin within 72 hours of first case notification. The primary outcome was the overall AR of suspected meningitis after inclusion. A random sample of 20 participating villages was enrolled to document any changes in fecal carriage prevalence of ciprofloxacin-resistant and extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae before and after the intervention. Between April 22 and May 18, 2017, 49 villages were included: 17 to the control arm, 17 to household prophylaxis, and 15 to village-wide prophylaxis. A total of 248 cases were notified in the study after the index cases. The AR was 451 per 100,000 persons in the control arm, 386 per 100,000 persons in the household prophylaxis arm (t test versus control p = 0.68), and 190 per 100,000 persons in the village-wide prophylaxis arm (t test versus control p = 0.032). The adjusted AR ratio between the household prophylaxis arm and the control arm was 0.94 (95% CI 0.52-1.73, p = 0.85), and the adjusted AR ratio between the village-wide prophylaxis arm and the control arm was 0.40 (95% CI 0.19â0.87, p = 0.022). No adverse events were notified. Baseline carriage prevalence of ciprofloxacin-resistant Enterobacteriaceae was 95% and of ESBL-producing Enterobacteriaceae was >90%, and did not change post-intervention. One limitation of the study was the small number of cerebrospinal fluid samples sent for confirmatory testing. CONCLUSIONS: Village-wide distribution of single-dose oral ciprofloxacin within 72 hours of case notification reduced overall meningitis AR. Distributions of ciprofloxacin could be an effective tool in future meningitis outbreak responses, but further studies investigating length of protection, effectiveness in urban settings, and potential impact on antimicrobial resistance patterns should be carried out. TRIAL REGISTRATION: ClinicalTrials.gov NCT02724046.
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Antibacterianos/uso terapéutico , Profilaxis Antibiótica/estadística & datos numéricos , Ciprofloxacina/uso terapéutico , Epidemias , Meningitis Meningocócica/tratamiento farmacológico , Meningitis Meningocócica/epidemiología , Administración Oral , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Meningitis Meningocócica/microbiología , Neisseria meningitidis/efectos de los fármacos , Neisseria meningitidis/fisiología , Niger/epidemiología , Adulto JovenRESUMEN
OBJECTIVES: The objectives of this study were to determine the rate of viral success in HIV-infected patients on first-line ART by the assessment of dried blood spot (DBS) viral load (VL) and to assess the performance of DBS sampling for VL measurement, genotypic resistance and antiretroviral concentration determinations. METHODS: HIV-infected patients treated for >1 year with first-line ART in Niamey, Niger were included. VL based on nucleic acid sequence-based amplification (NASBA) assay (limit of quantification <800 copies/mL) was measured on DBS capillary samples. Resistance genotype was assessed for all detectable VLs (limit of detection >100 copies/mL); antiretroviral concentrations were interpreted using standard plasma cut-offs after extrapolation of blood to plasma results. Median (IQR) results are presented. RESULTS: Two hundred and eighteen patients (61% women), aged 41 (34-46) years, with 138 (56-235) CD4 cells/mm3 at baseline were included. After 4 (2-6) years of follow-up under therapy, CD4 gain was +197 (98-372) cells/mm3; 81% had VL <800 copies/mL. Antiretroviral concentrations were adequate in 87% of patients and nevirapine/efavirenz concentrations were related to viral success (Pâ<â0.001). DBS genotypic resistance amplification succeeded in 71% of failing patients: NRTI drug resistance mutations were identified in 73% including resistance to lamivudine/emtricitabine (67%), abacavir (30%) and tenofovir (21%); and NNRTI drug resistance mutations were identified in 82% including resistance to rilpivirine (39%) and etravirine (15%). CONCLUSIONS: This study demonstrated a good response after 4 years of first-line ART in Niger. Adherence was high, according to antiretroviral concentrations, and the majority of failures were explained by selection of drug resistance mutations detected in the DBS genotype. Using DBS might improve the assessment of ART failure in HIV-infected patients in low-income countries.
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Antirretrovirales/uso terapéutico , Terapia Antirretroviral Altamente Activa , Sangre/virología , Infecciones por VIH/tratamiento farmacológico , VIH/aislamiento & purificación , Manejo de Especímenes/métodos , Carga Viral/métodos , Adolescente , Adulto , Antirretrovirales/farmacocinética , Análisis Químico de la Sangre , Estudios Transversales , Desecación , Femenino , Técnicas de Genotipaje/métodos , Humanos , Masculino , Cumplimiento de la Medicación , Pruebas de Sensibilidad Microbiana/métodos , Persona de Mediana Edad , Niger , Técnicas de Amplificación de Ácido Nucleico/métodos , Resultado del Tratamiento , Adulto JovenRESUMEN
Bordetella pertussis still poses an important health threat in developing countries. In Niger, notified pertussis cases are few despite the low diphtheria-tetanus-pertussis/pentavalent vaccine coverage. We aimed to estimate the prevalence of B. pertussis in children aged <5 years consulting at a pediatric ward. A 5-month study in 2011 recruited 342 children with respiratory symptoms at the National Hospital of Niamey. Nasopharyngeal aspirates were tested by culture and real-time polymerase chain reaction. Overall, 34 (11.2%) of the 305 available nasopharyngeal aspirates tested by real-time polymerase chain reaction were positive for a Bordetella spp., with an estimated prevalence of 8.2 cases per 1000 children aged <5. None was notified to the surveillance network. A single specimen was positive on culture. This study, the first to provide laboratory-confirmed data on pertussis in Niger, highlights the need to sensitize health care personnel to actively notify clinical cases and to integrate laboratory diagnosis in the existing surveillance system.
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Infecciones por Bordetella/epidemiología , Bordetella pertussis/aislamiento & purificación , Nasofaringe/microbiología , Adolescente , Infecciones por Bordetella/diagnóstico , Infecciones por Bordetella/microbiología , Bordetella pertussis/genética , Niño , Preescolar , ADN Bacteriano/análisis , ADN Bacteriano/genética , ADN Bacteriano/aislamiento & purificación , Femenino , Hospitales/estadística & datos numéricos , Humanos , Lactante , Masculino , Niger/epidemiología , Prevalencia , Estudios Prospectivos , Reacción en Cadena en Tiempo Real de la Polimerasa , Adulto JovenRESUMEN
Introduction and importance: Adrenal insufficiency is a rare chronic disease with a prevalence of 39 to 60 cases per million peoples in Europe. However, the prevalence is higher in sub-saharian Africa. The occurrence of pregnancy in adrenal insufficiency is rare but associated with high maternal and perinatal morbidity and mortality. For this reason, the management of pregnancy in adrenal insufficiency patient must be provided by a multidisciplinary team. Case presentation: The authors report the case of a 34-year-old pregnant woman followed for adrenal insufficiency secondary to prolonged corticosteroid therapy. Treatment consisted to an obstetrical and endocrinological follow-up and corticosteroid replacement therapy with hydrocortisone. A prophylactic cesarean section at 38 weeks resulted in the birth of a newborn male weighing 3395 g. Maternal and perinatal prognosis was good. Clinical discussion: Pregnancy in adrenal insufficiency is a therepeutic challenge in developing countries. Through this case, the authors discuss the therapeutic and prognostic aspects of adrenal insufficiency in our setting. Conclusion: With the introduction of gluco-corticosteroid replacement therapy, pregnancy in adrenal insufficiency can progress normally.
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BACKGROUND: Outcomes of retreatment for rifampicin-resistant tuberculosis (RR-TB) are rarely reported. We report 'definitive outcomes' after a cascade approach to RR-TB treatment. After a bacteriologically adverse outcome for the 9-months fluoroquinolone-based Short Treatment Regimen (STR), patients were retreated with a bedaquiline-based regimen (BDQ-regimen). METHODS: A Retrospective cohort study of RR-TB patients treated with the STR during 2012-2019 and retreated with a BDQ-regimen in case of failure or relapse was conducted. Definitive relapse-free cure took into account BDQ-regimen outcomes. RESULTS: Of 367 patients treated with the STR, 20 (5.4%) experienced failure or relapse. Out of these 20 patients, 14 started a BDQ-regimen, of whom none experienced failure or relapse. Definitive end of treatment outcomes of STR after revising with third-line BDQ-regimen outcomes, 84.7% (311/367) were cured relapse-free, 10.6% (39/367) died during treatment and 3.0% (11/367) were lost to follow-up during treatment with either the STR or BDQ-regimen. Six patients (1.6%; 6/367) with STR failure/relapse died before starting a BDQ-regimen. No patient had definitive treatment failure or relapse and remained without treatment. CONCLUSIONS: If fluoroquinolone resistance is excluded or rare, it is beneficial to use fluoroquinolone as the core drug for a first RR-TB treatment regimen and to safeguard bedaquiline for those in need of retreatment.
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Antituberculosos , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Antituberculosos/uso terapéutico , Rifampin/uso terapéutico , Estudios Retrospectivos , Niger , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Resultado del Tratamiento , Fluoroquinolonas/farmacología , Fluoroquinolonas/uso terapéuticoRESUMEN
BACKGROUND: Kidney transplantation is the treatment of choice for end-stage chronic kidney disease. It improves quality of life and increases life expectancy. At present, Niger is one of the poorest countries in the world does not practice kidney transplantation; thus, patients continue to be referred to other countries for transplantation. METHODS: This descriptive cross-sectional study was carried out at the Nephrology Department of the National Hospital Amirou Boubacar Diallo in Niamey, Niger over a 5-month period. It included all patients that had benefited from kidney transplantation with the aim to evaluate patient and graft survival. RESULTS: We identified 25 patients. The male to female ratio was 2:1. The average age was 45.4 years ± 11.1 years. The average age of donors was 36.1 years ± 12.6 years with a clear male predominance (17 males to 8 females); all of them were related-donors with 72% of them being brothers or sisters. The causative nephropathy was undetermined in 80% of patients. Sixty-four percent of patients had their kidney transplant in Maghreb, including 16% in Tunisia. The complications were mostly medical (68%), as 20% were immunologic; 8% infectious; 16% metabolic; 20% cardiovascular, and 4% were related to recurrence of the initial nephropathy. Surgical complications involved 6 patients (24%): 5 were vascular cases and one was a urological case. With a median follow-up of 5 years, the patients' survival was 84%, the graft survival was 56%, and death-censored graft survival was 67%. CONCLUSION: In Niger, after kidney transplantation, the patients' survival is satisfactory, whereas the graft survival is not, mostly due to inadequate follow-up check-ups and prohibitive prices of immunosuppressants.
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Enfermedades Renales , Fallo Renal Crónico , Trasplante de Riñón , Humanos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Trasplante de Riñón/efectos adversos , Niger , Estudios Transversales , Calidad de Vida , Enfermedades Renales/etiología , Fallo Renal Crónico/cirugía , Fallo Renal Crónico/etiología , Supervivencia de Injerto , Resultado del TratamientoRESUMEN
Measles is a rapidly growing disease in the world with 869,770 cases and 207,500 deaths recorded in 2019. Niger continues to record epidemic outbreaks despite the actions taken. This study aims to analyze the national database from 2010 to 2019 to characterize the epidemiology of measles in Niger. This is a descriptive retrospective study. Our sample is exhaustive of suspected and positive measles cases from the database of the department of surveillance and response to epidemics for 10 years. Data extraction and analysis was done using Epi Info 7.2.3.1 software. In our study we found n=11,784 suspected measles cases notified from 2010 to 2019 with 37.2% of positive cases (IgM+). All regions are concerned. The female/male sex ratio was 1.1. The 1-to-5-year age group was the most representative (44.44%); 28.3% received at least one dose of vaccine; 62.22% lived in urban areas. The number of deaths was 225 (1.9%). The proportion of samples received at the laboratory within 3 days is 70.38%. The baseline analysis allowed us to find that all regions recorded cases and deaths with a low vaccination rate of 28.3%. Improved response and immunization strategies are recommended.
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Asteraceae , Sarampión , Femenino , Masculino , Humanos , Niger/epidemiología , Estudios Retrospectivos , Sarampión/epidemiología , VacunaciónRESUMEN
BACKGROUND: Rifampicin-resistant tuberculosis (RR-TB) treatment requires combination treatment, which frequently causes serious adverse events and globally results in not much more than 60% treatment success. In Niger, a high cure rate was obtained with a RR-TB treatment strategy based on a second-line injectable drug (SLID)-containing Short Treatment Regimen (STR), with linezolid replacing the SLID in patients with ototoxicity. Given the availability of novel anti-tuberculosis drugs, WHO recommends all-oral RR-TB treatment. Considering the high level of success with the Niger treatment strategy, it would only be justified to replace it in case robust evidence shows that the WHO all-oral bedaquiline/linezolid (BDQ/LZD)-containing STR (experimental arm) performs better than the Niger RR-TB treatment strategy, (control arm) in terms of safety, effectiveness and adherence. METHODS: A pragmatic randomised clinical trial (RCT) using stratified block randomisation, conducted between April 2021 and March 2024, prospectively enrols participants diagnosed with RR-TB in one of the four RR-TB units of the nation. Depending of the month in which patients are diagnosed with RR-TB, patients with FQ-susceptible RR-TB are enrolled in either the experimental arm or control arm. DISCUSSION: To increase the feasibility of conducting a RCT, embedded in routine activities of all Niger's RR-TB Units, we used a creative trial design. We randomised by monthly blocks, whereby the regimen used changes every month, using the month of RR-TB diagnosis as stratifying variable. This approach was deemed feasible for Niger's national tuberculosis programme, as it simplifies the work of the clinicians running the RR-TB units. Our creative design may serve as an example for other national programs. Findings will inform national and international RR-TB treatment guidelines, and will also strengthen the evidence-base on how to develop robust RR-TB treatment regimens. TRIAL REGISTRATION: Pan African Clinical Trial Register PACTR202203645724919 . Registered on 15 March 2022.
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Tuberculosis Resistente a Múltiples Medicamentos , Tuberculosis Pulmonar , Humanos , Rifampin/efectos adversos , Linezolid/efectos adversos , Tuberculosis Pulmonar/diagnóstico , Niger , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Antituberculosos/efectos adversos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
The effectiveness of artemisinin-based combination therapies (ACTs) depends not only on that of artemisinin but also on that of partner molecules. This study aims to evaluate the prevalence of mutations in the Pfdhfr, Pfdhps, and Pfmdr1 genes from isolates collected during a clinical study. Plasmodium genomic DNA samples extracted from symptomatic malaria patients from Dogondoutchi, Niger, were sequenced by the Sanger method to determine mutations in the Pfdhfr (codons 51, 59, 108, and 164), Pfdhps (codons 436, 437, 540, 581, and 613), and Pfmdr1 (codons 86, 184, 1034, and 1246) genes. One hundred fifty-five (155) pre-treatment samples were sequenced for the Pfdhfr, Pfdhps, and Pfmdr1 genes. A high prevalence of mutations in the Pfdhfr gene was observed at the level of the N51I (84.97%), C59R (92.62%), and S108N (97.39%) codons. The key K540E mutation in the Pfdhps gene was not observed. Only one isolate was found to harbor a mutation at codon I431V. The most common mutation on the Pfmdr1 gene was Y184F in 71.43% of the mutations found, followed by N86Y in 10.20%. The triple-mutant haplotype N51I/C59R/S108N (IRN) was detected in 97% of the samples. Single-mutant (ICS and NCN) and double-mutant (IRS, NRN, and ICN) haplotypes were prevalent at 97% and 95%, respectively. Double-mutant haplotypes of the Pfdhps (581 and 613) and Pfmdr (86 and 184) were found in 3% and 25.45% of the isolates studied, respectively. The study focused on the molecular analysis of the sequencing of the Pfdhfr, Pfdhps, and Pfmdr1 genes. Although a high prevalence of mutations in the Pfdhfr gene have been observed, there is a lack of sulfadoxine pyrimethamine resistance. There is a high prevalence of mutation in the Pfmdr184 codon associated with resistance to amodiaquine. These data will be used by Niger's National Malaria Control Program to better monitor the resistance of Plasmodium to partner molecules in artemisinin-based combination therapies.
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This study aims to evaluate the factors influencing the adherence to the 2nd and 3rd doses of Amodiaquine (AQ) during seasonal malaria chemoprevention (SMC) in Burkina Faso, Mali, and Niger. Overall, 3132 people were interviewed during surveys between 2019 and 2020 in 15 health districts. In Burkina Faso, Mali, and Niger, the proportions of non-adherence were 4.15%, 5.60%, and 13.30%, respectively, for the 2nd dose and 3.98%, 5.60% and 14.39% for the 3rd dose. The main cause of non-adherence to the 2nd and 3rd doses was other illnesses in 28.5% and 29.78%, respectively, in Burkina Faso, 5.35% and 5.35% in Mali and 1.6% and 0.75% in Niger. It was followed by vomiting in 12.24% and 10.63% for Burkina and 2.45% and 3.78% in Niger. The last cause was refusal in 6.12% and 4.25% in Burkina, 33.9% and 15.25% in Mali and 0.8% and 1.51% in Niger. Non-adherence of doses related to parents was primarily due to their absence in 28.5% and 27.65% in Burkina, 16.07% and 16.07% in Mali and 7.37% and 6.06% in Niger. Traveling was the second cause related to parents in 12.24% and 12.76% in Burkina, 19.64% and 19.64% in Mali and 0.81% and 0.75% in Niger. Non-adherence related to community distributors was mainly due to missing the doses in 4.08% and 4.25% in Burkina, 23.21% and 23.21% in Mali, 77.04% and 76.51% in Niger. Our study reported very small proportions of non-adherence to 2nd and 3rd doses of SMC and identified the main causes of non-adherence. These findings will provide helpful information for policymakers and public health authorities to improve adherence to SMC.
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This prospective study included 35 patients suffering from Graves' disease (GD) clinically and biologically confirmed by endocrinologists, sent to the nuclear medicine department of CHU de Bab El Oued, Algiers for iodine-131 therapy. CHU de Bab El Oued is a tertiary hospital located in the center of the capital Algiers. The aim of this study is to propose a simplified dosimetric procedure which will initiate iodine-131 therapy of GD in particular and hyperthyroidism in general in Niger. The determination of the maximum uptake was performed with a Biodex external probe at 2 h, 4 h, and 24 h after the administration of 3 MBq of liquid iodine-131. The iodine-131 activities were determined using the Marinelli formula with a predefined effective half-life (Te) of 5 days and subsequently extrapolated half-life with kaleidagraph software. The statistical analysis was performed using an excel sheet and analyzed using the software package Statistica 10 (stat Soft, Tulsa, USA). the male:female gender ratio was1:4.5 and the mean age was 42.56 years (±7.14). The body mass index was within normal range with a value of 25.25 kg2(±0.42) and the mean average thyroid mass was equal to 24.05 (±10.53) g. The mean uptake value at 24 h was 43.24% (±17.68%) meanwhile the maximum uptake value was 46.28 (±21.13%). The estimated effective half-life (Te) was 5.44 days (±1.96) days which were different from the predefined Te of 5 days. The mean activity determined with fixed Te and 24 h uptake was 244.45 (±109.2) MBq and the mean activity calculated with both extrapolated Te and maximum uptake was 452.22 (±381.9) MBq. Empirical determination of activity in the treatment of GD gives higher activities (1.5 times) to patients than dosimetric methods based on the determination of extrapolated effective half-life.
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INTRODUCTION: COVID-19 has spread across the African continent, including Niger. Yet very little is known about the phenotype of people who tested positive for COVID-19. In this humanitarian crises region, we aimed at characterizing variation in clinical features among hospitalized patients with COVID-19-like syndrome and to determine predictors associated with COVID-19 mortality among those with confirmed COVID-19. METHODS: The study was a retrospective nationwide cohort of hospitalized patients isolated for COVID-19 infection, using the health data of the National Health Information System from 19 March 2020 (onset of the pandemic) to 17 November 2020. All hospitalized patients with COVID-19-like syndrome at admission were included. A Cox-proportional regression model was built to identify predictors of in-hospital death among patients with confirmed COVID-19. RESULTS: Sixty-five percent (472/729) of patients hospitalized with COVID-19 like syndrome tested positive for SARS-CoV-2 among which, 70 (15%) died. Among the patients with confirmed COVID-19 infection, age was significantly associated with increased odds of reporting cough (adjusted odds ratio [aOR] 1.02; 95% confidence interval [CI] 1.01-1.03) and fever/chills (aOR 1.02; 95% CI 1.02-1.04). Comorbidity was associated with increased odds of presenting with cough (aOR 1.59; 95% CI 1.03-2.45) and shortness of breath (aOR 2.03; 95% CI 1.27-3.26) at admission. In addition, comorbidity (adjusted hazards ratio [aHR] 2.04; 95% CI 2.38-6.35), shortness of breath at baseline (aHR 2.04; 95% CI 2.38-6.35) and being 60 years or older (aHR 5.34; 95% CI 3.25-8.75) increased the risk of COVID-19 mortality two to five folds. CONCLUSION: Comorbidity, shortness of breath on admission, and being aged 60 years or older are associated with a higher risk of death among patients hospitalized with COVID-19 in a humanitarian crisis setting. While robust prospective data are needed to guide evidence, our data might aid intensive care resource allocation in Niger.